Molecular BioSystems will be publishing a themed issue on proteomics in 2015.

Please e-mail the Editorial Office if you are interested in contributing an article. The Guest Editor for this issue is Professor Massimo Castagnola of The Italian Proteomics Association.

We invite scientists in the field of proteomics and integrative biology to contribute to this themed issue dedicated to these rapidly developing topics. It will be a comprehensive collection of papers that showcases the rapid advances in the proteomics field.

Both research Papers, and Communication are welcome to this issue – these must be within the scope of issue and be of the highest quality.

Please note that the deadline for submissions is 19 December 2014

Manuscripts can be submitted using the our online article submission service. Please clearly state that the manuscript is submitted in response to the call for papers for the themed issue on Proteomics.

All submissions will be subject to the normal peer review procedures of Molecular BioSystems.

Everyone at Molecular BioSystems would like to warmly welcome Dr Lyn Jones to his new role on the journal’s Editorial Board.

Lyn received his undergraduate education at the University of Bath and then completed PhD studies with Prof. Alan Armstrong at the University of Nottingham in synthetic organic chemistry. He then started his post doctorate research with Prof. Kim Janda at The Scripps Research Institute, California in the area of chemical biology. In 2001, he joined Pfizer in Sandwich, UK as a medicinal chemistry team leader and his contributions to the early clinical portfolio were recognised with the inaugural Royal Society of Chemistry Young Industrialist of the Year Award in 2009.

He recently transferred to Cambridge, Massachusetts to lead the Chemical Biology and Rare Diseases Chemistry groups in Pfizer. His research interests include the development of novel chemoproteomic technologies that report on target engagement in intact cells, and the use of medicinal chemistry to advance biotherapeutic modalities. He is a Fellow of the Royal Society of Chemistry (FRSC) and the Society of Biology (FSB), and is an elected member of the Chemistry-Biology Interface Division of the RSC. Recently, he was also a Guest Editor for a themed issue on Chemical Biology for Target Identification and Validation in our sister MedChemComm.

“It’s an honour to join the board of this prestigious journal, which has become essential reading for those working at the interface of chemistry and biology. In particular, I’m very keen to see the inevitable growth in the application of chemical biology research within the drug discovery setting, and MBS is ideally poised to share these advances with a wide audience.” - Lyn Jones

Published on behalf of Kelly Theisen, web writer for Molecular BioSystems and Integrative Biology

Beta-amyloid (Aβ) aggregates are infamous for forming the toxic plaques in the brain of Alzheimer’s disease patients. The detrimental effects are fairly well studied, but the mechanism of formation remains largely a mystery.

Now, thanks to Ifor D. W. Samuel, J. Carlos Penedo and colleagues at University of St. Andrews and Glasgow University, researchers have a new fluorescent probe to study the process of Aβ aggregation. This paper was featured on the cover of the January 2014 issue of Molecular Biosystems.

The most common probe of Aβ currently in use is Thioflavin T (ThT), which has been very successful at detecting the presence of aggregates. However, this probe has a limited pH range where it can be used. Aggregate structures can form at low concentrations of Aβ, and in the slightly acidic (pH = 6) endosome, but both of these are beyond the detection limits of ThT. For maximum utility, a probe would be able to track Aβ formation under any biological conditions.

Fig 1: Representative aggregation time course and relative fluorescence quenching during the HFIP-induced aggregation of Ab1–42

To address this disadvantage, Samuel & Penedo et al. have used a HiLyte Fluorescent probe attached to the N-terminal position of Aβ monomers. When monomers associate with each other, the probe undergoes fluorescence self-quenching (FSQ), a well-documented process where the presence of two probes proximal to each other will cause a decrease in the observed fluorescent signal. This decrease in signal can be monitored and correlated with the aggregation rate and type of Aβ structure formed.

First the researchers determined that the probe did not affect the final Aβstructures obtained by a TEM image comparison to ThT Aβ under various conditions (see Figure 1 below). They also showed that the rate of Aβ formation stayed the same. Because the HiLyte probe does not affect the normal Aβ function, they could then use the probe under biological conditionsnot accessible to ThT.

They found that they were able to detect fibrils under biological conditions (Figure 2a below), oligomers under endosomal conditions (Figure 2bbelow) and ADDLs (early precursor structures that occur at low Aβ concentrations). Each of these Aβstructures produced a different fluorescent signature, allowing them to be distinguished from each other. This ability to detect the different Aβ assembly rates will allow researchers to better characterize biological samples, hopefully leading to new treatment options for Alzheimer’s disease.

Published on behalf of Kelly Theisen, web writer for Molecular BioSystems and Integrative Biology

Dr. Saini and colleague at the Indian Institute of Technology, Bombay have used a mathematical model to track the gene expression pathway of a bacterium that causes whooping cough (or pertussis). The understanding of gene regulation along the growth and infection process for Bordetella could lead to new ways to block its action.

The Bordetella bacterium colonizes the respiratory tracts of several hosts, including humans, to cause the infection most commonly referred to as whooping cough. There are two stages of the infection, with the first being mild (cold like symptoms), followed by the intense coughing and difficulty breathing which creates the characteristic “whooping” sound for which the infection is named. This second stage of the infection is controlled by a specific set of genes in the bacterium DNA, and regulated by one pathway known as BvgAS.

This pathway BvgAS is a series of three phosphorylation reactions, where a phosphate group is added to specific proteins in turn, and the final protein then activates the genes responsible for virulence (infection). The addition or removal of a phosphate group is a standard way for cells to turn proteins “on” or “off” as needed. Figure 1 below shows the activation pathway of the final protein in the series (BvgA, triangle), which is the gene promoter.

Figure 1

The researchers were able to recover experimentally observed gene activation for four important classes of genes. They monitored where the pathway of interest changes from a repressed state (i.e. genes are inactive, or unexpressed), to an intermediate state, and finally to an active state (i.e. genes are expressed). The expression levels for each class of genes observed during the transitions are shown in Fig. 2 below.

Additionally, the same simulations were carried out on mutant bacteria containing one phosphorylation event in the pathway. This was done to understand the role of having three phosphorylation reactions for BvgAS, while typical pathways in bacteria have one or two events. This extra complexity was found to provide the bacterium with sensitivity and flexibility to respond to environmental factors, by changing the gene expression profile.

Understanding how the bacterium can respond to changing environmental factors by regulating gene expression could lead to new treatments for the infection in humans.

Figure 2

Read the full HOT paper by Mahendra Kumar Prajapa and Supreet Saini here: